PROJECT SUMMARY Candidate: Dr. Jonathan Casey MD, MSCI is an Assistant Professor at Vanderbilt University Medical Center. Dr. Casey has a strong background in clinical trials of critically ill adults obtained through formal training in clinical research and the conduct of comparative effectiveness trials of respiratory support. His long-term career plan as a physician scientist is to become recognized as a leader in the conduct of pragmatic trials of early respiratory support in critically ill adults. To achieve this, his immediate goals are to adapt the pragmatic trial methodology he has used in the intensive care unit to the chaotic environment of the emergency department, become an expert in the forms of consent used in emergency research, gain experience applying tools from implementation science to improve the quality of pragmatic trials, and learn the advanced modeling methods required for enriching clinical trials and analyzing of heterogeneity of treatment effect. Research Project: Each year more than 1.5 million critically ill patients receive mechanical ventilation in the United States, and the placement of an endotracheal tube for mechanical ventilation in critically ill patients is fraught with complications with one-in-five experiencing hypoxemia and one-in-forty experiencing cardiac arrest. Bag-mask ventilation has been shown to prevent life-threatening hypoxemia among patients in the ICU, but it is unclear if these results generalize to the ED and pre-hospital setting, where the majority of critically patients are intubated. Due to differences in patient populations, patients in the ED are, on average, at lower risk for peri-intubation hypoxemia and higher risk of aspiration (a proposed risk of bag-mask ventilation), and bag-mask ventilation is rarely used in this setting. Improved understanding of the risks and benefits of bag- mask ventilation during tracheal intubation in the ED is urgently needed. The Specific Aims of the proposed research are: Aim 1) Develop a model to estimate the lowest oxygen saturation during tracheal intubation in the ED; and Aim 2) Use the model from Aim 1 for prognostic enrichment, selectively enrolling patients at risk for hypoxemia into the SAFEty of bag-mask VENTilation in the ED (SAFEVENTED) study, a 464-patient randomized trial testing the hypothesis that bag-mask ventilation will increase the lowest oxygen saturation of patients undergoing intubation in the emergency department. Career Development: Dr. Casey's career development plan integrates coursework, experiential learning, and training with his mentors to: 1) learn the modeling techniques required to develop and analyze the SAFE- VENTED trial; 2) develop expertise in EFIC and other forms of consent used in emergency care research; and 3) leverage tools from implementation science to improve delivery of trial interventions during pragmatic trials. Environment: As a supportive and well-resourced institution with international leaders in clinical trials, emergency care research, human subjects protection, bioinformatics, and biostatistics, Vanderbilt is the ideal environment to foster Dr. Casey's development into a national leader in trials of early respiratory support.